Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

The invading front of malignant tumors is a source of prognostic information

T Goldmann PhD 1, L Suter MD 2, D Ribbert PhD 3, F Witt MD 4, A Moorkamp MD 5, E Vollmer MD 1, F Otto PhD 2

1 Klin & Exp Pathologie, Forschungszentrum Borstel, Borstel, Germany;, 2 Fachklinik Hornheide; © Allgemeine Zoologie und Genetik, Universityät Münster;, 4 Abteilung Strahlentherapie, Universityätsklinikum Münster; Münster, Germany, 5 Sankt Bernhard Hospital, Kamp-Lintfort, Germany,

AIMS: To identify prognostic markers for metastasis at the stage of primary tumor excision, we retrospectively analyzed the expression of different proteolytic enzymes in formalin-fixed, paraffin-embedded specimen from human primary cutaneous melanomas, squamous cell carcinomas of the skin as well as a small collection of prostate carcinomas (radical prostatectomies) along with clinical and histological data. METHODS: We compared the expression of proteolytic enzymes in tumors that metastasized and tumors that did not during the follow up period of at least 5 years by means of immunohistochemistry. RESULTS: In cutaneous melanomas (pT3 and pT4, N=147) we found statistically significant differences in the expression of the three proteolytic enzymes cathepsin b, cathepsin d and collagenase IV at the dermal invading front of the tumors: metastasized melanomas showed higher scores. The predictive value of the expression of all three enzymes was higher compared to the established risk factor tumor thickness. In squamous cell carcinomas of the skin (N=53, no analysis of cathepsin b) only the expression of cathepsin d at the invading front of the tumor as well as the cathepsin d overall expression was significantly different between the tumors that metastasized and tumors that did not. The same applies to prostate carcinomas (N=17). Combined risk factor scores led to extended predictive capabilities in all three types of tumors. CONCLUSIONS: The expression of proteolytic enzymes at the invading front of malignant tumors delivers prognostic information for the prediction of metastasis, which may lead to earlier treatment of risk patients. Prospective studies are underway.

KEY WORDS: melanoma, squamous cell carcinoma, prostate carcinoma, immunohistochemistry, prognostics.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on prognostic markers.